2. Academic Validation
  3. Microbial transformation of pentacyclic triterpenes for anti-inflammatory agents on the HMGB1 stimulated RAW 264.7 cells by Streptomyces olivaceus CICC 23628

Microbial transformation of pentacyclic triterpenes for anti-inflammatory agents on the HMGB1 stimulated RAW 264.7 cells by Streptomyces olivaceus CICC 23628

  • Bioorg Med Chem. 2021 Dec 15;52:116494. doi: 10.1016/j.bmc.2021.116494.
Yuyuan Zhu 1,  Pingping Shen 1,  Jiayi Wang 1,  Xuewa Jiang 1,  Wei Wang 1,  Richa Raj 1,  Haixia Ge 2,  Weiwei Wang 3,  Boyang Yu 4,  Jian Zhang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
  • 2 School of Life Sciences, Huzhou University, Huzhou 313000, PR China.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, PR China.
  • 4 Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, PR China.
  • 5 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, PR China; ZhenPing Expert Workstation for Zhang Jian, Zhenping, Ankang, Shaanxi 725699, PR China. Electronic address: [email protected].
PMID: 34800877 DOI: 10.1016/j.bmc.2021.116494
Abstract

High mobility group box-1 protein (HMGB1) is a typical Damage-Associated Molecular Patterns (DAMPs) released in response to cellular inflammation. The pentacyclic Triterpenes (PTs) are considered to be the natural inhibitors against HMGB1-related inflammation. To explore new lead compounds of PTs as anti-inflammatory agents, biotransformation of four PTs by Streptomyces olivaceus CICC 23628 was investigated in this study. As a result, thirteen unique 3,4-seco-triterpenes metabolites were isolated and twelve of them were first identified and reported. Structures of metabolites were determined based on HR-ESI-MS, 1D/2D NMR, and single-crystal X-ray diffraction. Furthermore, all compounds were subjected to the bioassay on the model of HMGB1-stimulated RAW 264.7 cells to evaluate their anti-inflammatory activity through nitric oxide (NO) inhibition activity. Compounds 3b (3,4-seco-olean-12-en-4,21α,22β,24-tetrahydroxy-ol-3-oic acid) and 2b (3,4-seco-olean-12-en-4,21β,22β,24,29-pentahydroxy-ol-3-oic acid) exhibited NO inhibitory activity with IC50 values of 15.94 μM and 36.00 μM, respectively. Thus, indicating their potential as HMGB1 inhibitors and in developing potent anti-inflammatory agents. This work provides an operationally simple, efficient method for the rapid diversification of the PTs scaffold for a variety of distinctive 3,4-seco-triterpenes to facilitate the discovery of potential anti-inflammatory compounds.

Keywords

3,4-seco-triterpenes; Anti-inflammatory activity; Biotransformation; High mobility group box-1 protein; Pentacyclic triterpenes; Streptomyces olivaceus CICC 23628.

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